{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:58:59Z","timestamp":1791403139983,"version":"4.3.3"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JOR Spine"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Intervertebral disc degeneration (IVDD) is the leading cause of low back pain, and apoptosis plays a key role in its pathogenesis. Distal\u2010less homeobox 5 (Dlx5) has been reported to induce cell apoptosis. Melatonin, as a powerful antiapoptotic agent, has been widely reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>This study aimed to investigate the role of DLX5 in the pathogenesis of IVDD and the potential therapeutic role of melatonin in targeting DLX5 in IVDD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials &amp; Methods<\/jats:title><jats:p>Western blotting, RT\u2013qPCR, immunohistochemistry, si\u2010DLX5, Ex\u2010DLX5, flow cytometry, and immunofluorescence were used to examine the regulatory effect of DLX5 on apoptosis. Therapeutic efficacy was assessed by the intraperitoneal injection of melatonin into IVDD mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The expression level of DLX5 is significantly increased in IVDD, and the expression levels were positively correlated with the grade of IVDD. DLX5 was significantly upregulated in TNF\u2010\u03b1\u2010induced degenerative NP cells. Degenerative NP cells transfected with si\u2010DLX5 exhibited significantly less apoptosis than control cells. Melatonin significantly alleviated IVDD in surgically induced IVDD model mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The results revealed that the expression of DLX5 was positively correlated with the severity of IVDD and that melatonin ameliorated DLX5\u2010induced apoptosis and extracellular matrix imbalance by inhibiting the TGF\u2010\u03b2\/Smad signaling pathway. This study may provide therapeutic strategies to alleviate inflammation\u2010induced apoptosis IVDD\u2010associated inflammation\u2010induced apoptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>DLX5 plays an important role in IVDD progression by promoting apoptosis, and melatonin represents a promising therapeutic strategy for alleviating IVDD\u2010associated inflammation and apoptosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jsp2.70014","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T12:34:45Z","timestamp":1731501285000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Melatonin attenuates degenerative disc degression by downregulating <scp>DLX5<\/scp> via the <scp>TGF<\/scp>\/Smad2\/3 pathway in nucleus pulposus cells"],"prefix":"10.1002","volume":"7","author":[{"given":"Kuibo","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Spine Surgery The Fifth Affiliated Hospital of Sun Yat\u2010sen University  Zhuhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery The First Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Mo","sequence":"additional","affiliation":[{"name":"The Third Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"Guangdong Research Institute for Orthopedics &amp; Traumatology of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Huang","sequence":"additional","affiliation":[{"name":"Laboratory of General Surgery, The First Affiliated 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